Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene

Christian J. Gaffney, Tsutomu Oka, Virginia Mazack, Dror Hilman, Uri Gat, Tomoki Muramatsu, Johji Inazawa, Alicia Golden, David J. Carey, Amjad Farooq, Gerard Tromp, Marius Sudol*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

The YAP1 gene encodes a potent new oncogene and stem cell factor. However, in some cancers, the YAP1 gene plays a role of tumor suppressor. At present, the gene and its products are intensely studied and its cDNAs are used as transgenes in cellular and animal models. Here, we report 4 new potential mRNA splicing isoforms of the YAP1 gene, bringing the total number of isoforms to 8. We detected all 8 YAP1 isoforms in a panel of human tissues and evaluated the expression of the longest isoform of YAP1 (YAP1-2δ) using Real Time PCR. All YAP1 isoforms are barely detectable in human leukocytes compared to fair levels of expression found in other human tissues. We analyzed the structure of the genomic region that gave rise to alternatively spliced YAP1 transcripts in different metazoans. We found that YAP1 isoforms, which utilize exon 6 emerged in evolution with the appearance of amniotes. Interestingly, 6 YAP1 isoforms, which contain the exon 5 extension, exon 6 or both would have their leucine zipper region disrupted in the predicted protein product, compared to the intact leucine zipper found in two YAP1 (α) isoforms. This observation has direct functional ramifications for YAP1 signaling. We also propose a normalized nomenclature for the mRNA splice variants of the YAP1 gene, which should aid in the characterization of signaling differences among the potential protein products of the YAP1 gene.

Original languageAmerican English
Pages (from-to)215-222
Number of pages8
JournalGene
Volume509
Issue number2
DOIs
StatePublished - 10 Nov 2012

Bibliographical note

Funding Information:
We thank our colleagues Kristin Berger, Kieran Harvey, Nikos Tapinos and Greg Yochum for valuable comments on the first version of the manuscript. This work was supported by PA Breast Cancer Coalition Grants (# 60707 and # 920093 ) plus the Geisinger Clinic (to MS) and by funds from the National Institutes of Health (Grant# R01-GM083897 ) and the USylvester Braman Family Breast Cancer Institute to AF.

Keywords

  • Alternative splicing
  • Leucine zipper
  • Quantitative RT-PCR
  • WW domains

Fingerprint

Dive into the research topics of 'Identification, basic characterization and evolutionary analysis of differentially spliced mRNA isoforms of human YAP1 gene'. Together they form a unique fingerprint.

Cite this